Photodynamic therapy involves the application of light to abnormal tissues (referred to herein as "lesions") in or on the body of a human or other mammalian subject to cause regression of the lesion. Ordinarily, a drug which increases the sensitivity of bodily tissues to light, referred to herein as a "photosensitizing agent" is administered before exposure of the tissues to light. When the light is applied to the tissues, chemical reactions which disrupt the normal function of the cells occur. This kills the tissues constituting the lesions. This process is applied, for example, in treatment of skin cancer and cancer of the internal organs. Preferred photosensitizing agents such as porphyrins tend to concentrate in cancerous tissues and increase the sensitivity of the cancerous lesion to light to a far greater degree than the increased sensitivity of the surrounding normal tissues. Thus, the cancerous lesion can be killed without destroying all of the surrounding normal tissues. The practice of photodynamic therapy is described, for example, in the article "Photodynamic Therapy in Oncology: Methods and Clinical Use", J. National Cancer Institute, Vol. 85, No. 6, pp. 443-456, March, 1993.
The treatment light used to perform photodynamic therapy commonly is administered through a hand-held device which is aimed by the physician during the treatment. For example, the light may be produced by a laser and guided through an optical fiber to a probe held by the physician. The physician can apply the light to the lesion by visually guiding the probe over the lesion. This approach works well for small, localized lesions. However, it necessarily depends upon the skill of the physician in observing the lesion and guiding the instrument. While some lesions are readily distinguishable from the surrounding tissue using ordinary visual observation, others are not. Also, where the lesions are widespread and located in an area with complex internal anatomy, it is difficult to direct the light onto all of the lesions. It is, therefore, likely that some lesions will remain untreated.
One approach which has been used to avoid these difficulties is simply to apply the treating light widely, on all of the tissues in the vicinity of the lesions. For example, as described in Tockner et al., Intrathoracic Photodynamic Therapy: A Canine Normal Tissue Tolerance Study and Early Clinical Experience, Lasers In Surgery and Medicine, 14:118-123 (1994) and in Pass et al., Use of Photodynamic Therapy for the Management of Pleural Malignancies, Seminars in Surgical Oncology 11:360-367 (1995), the treating light may be diffused throughout the surrounding tissues by filling an intrabody cavity with a light diffusing medium such as a liquid solution and directing the light into this diffusing medium. The light-directing instrument is also equipped with a diffusing optical system. This approach assures that the treating light will be delivered to all of the lesions. However, the treating light necessarily is also administered to surrounding normal tissues. Therefore, the dose of treating light which can be administered is limited to the dose which can be tolerated by the surrounding normal tissue.
Other proposals have been advanced for administering treating light in photodynamic therapy by means of light-emitting devices disposed within the body. Thus, Chen et al., U.S. Pat. No. 5,571,152 recites a "microminiature illuminator" with a light emitting diode and miniature microwave antennas. The microminiature illuminator assertedly can be injected into the interior of a tumor and can be actuated by RF power applied through the patient's tissues causing the LED to emit light within the tumor. Chen et al., U.S. Pat. No. 5,445,608, teaches other devices for PDT, including elongated probes with numerous LEDs thereon and a flat panel with multiple light emitting "vertical cavity surface-emitting lasers or," also referred to as "VCSELs" According to the '608 patent, multiplexing the VCSELs in time so that less than all sixteen are energized simultaneously minimizes the instantaneous current drawn by the devices. The devices have not been widely adopted in the art.
Other workers have sought to monitor the effectiveness of photodynamic therapy. Thus, Dorian, U.S. Pat. No. 5,533,508 and U.S. Pat. No. 5,572,996 disclose that tissues treated with photosensitizers will fluoresce when irradiated with the treatment light and that this fluorescence can be used as a measure of the efficacy of the treatment. Thus, when tissue treated with the sensitizer Photofrin-II is illuminated with treating light at 630 nm, the tissue will flouresce at about 690 nm and this fluorescence can be detected and used as a measure of the efficacy of the treatment.
Nonetheless, still further improvements in apparatus and methods for delivering photodynamic therapy would be desirable. It would be desirable to provide apparatus and methods which will concentrate the treating light on the lesion rather than on the surrounding normal tissues, without depending entirely on the skill and attention of the physician to accomplish this result.